Short hairpin RNA targeting survivin inhibits growth and angiogenesis of glioma U251 cells.
Short hairpin RNA targeting survivin inhibits growth and angiogenesis of glioma U251 cells.
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DOI：
10.3892/ijo.31.5.1111
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发表时间：
2007-11
影响因子：
5.2
通讯作者：
H. Zhen;Li-wen Li-Li-wen-Li-2145535296;Wei Zhang;Z. Fei;C. Shi;Tong-tao Yang;Wenjie Bai;Xiang Zhang
中科院分区：
文献类型：
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作者：
H. Zhen;Li-wen Li-Li-wen-Li-2145535296;Wei Zhang;Z. Fei;C. Shi;Tong-tao Yang;Wenjie Bai;Xiang Zhang
Survivin是一种新的肿瘤相关基因，其过表达与肿瘤的发生、发展密切相关。然而，存活素在胶质瘤发生和发展中的确切作用仍不完全清楚。我们构建了三个靶向survivin的短发夹RNA（shRNA）质粒载体，并将它们导入胶质瘤U251细胞。这三种shRNAs能够有效和特异性地敲低瞬时转染的U251细胞中survivin的表达。稳定表达对Survivin具有最强抑制作用的shRNA的转染子表现出细胞生长下降，自发凋亡增加，有丝分裂灾难和细胞周期停滞。此外，在裸鼠异种移植物中，稳定的转染子呈现减少的从头胶质瘤形成和减少的血管生成的发展。本研究结果表明，Survivin在胶质瘤的恶性增殖、抗凋亡和血管生成中起重要作用，有望成为胶质瘤基因治疗的新靶点，而shRNA介导的RNA干扰（RNAi）有望成为肿瘤基因治疗的新策略。
Survivin is a novel tumor-associated gene, its overexpression mostly associates with carcinogenesis and development. Nevertheless, the precise role of survivin in initiation and progression of gliomas is still not completely clear. We constructed here three short hairpin RNA (shRNA) targeting survivin plasmid vectors and introduced them into glioma U251 cells. The three shRNAs were efficiently and specifically able to knockdown the survivin expression in transiently transfected U251 cells. The stable transfectants expressing the shRNA having the strongest inhibitory effect against survivin exhibited decreased cell growth, increased spontaneous apoptosis, mitotic catastrophe and cell cycle arrest. Furthermore, in nude mice xenografts, the stable transfectants presented decreased de novo glioma formation and reduced development of angiogenesis. Results from this study indicate that survivin plays an important role in malignant proliferation, antiapoptosis and angiogenesis of gliomas, which may become an attractive target for gene therapy of gliomas, while RNA interference (RNAi) mediated by shRNA may become a new promising strategy for cancer gene therapy.